Cerebrovascular disease is a major cause of dementia and is potentially preventable. However, vascular dementia is poorly characterized and its true prevalence is unknown. Controversies in the understanding of vascular dementia relate to the mechanisms by which stroke affects cognition, the clinical features that distinguish vascular dementia from Alzheimer's disease, the role of cerebral white matter changes in presaging "brain t risk" for ischemic damage, and the size and location of cerebral infarcts necessary to produce cognitive impairment. Prospective studies of the clinical, neuropsychological, neuro-imaging, and neuropathological correlates of stroke and cognition are needed. This application addresses that need by longitudinally studying subjects at high risk for cerebral ischemic infarction on cognitive and behavioral measures. These measures have been validated in longitudinal studies of demented and nondemented elderly persons and will be obtained annually. They include clinical and psychometric methods that tap a wide range of cognitive abilities (verbal and nonverbal memory; intelligence; visuospatial and psychomotor abilities; language). An experimental neuropsychological battery will measure subtle deficits produced by unilateral hemispheric lesions. Cerebral hemodynamic studies at entry will evaluate increased regional oxygen extraction fraction as a potential marker for cerebral areas at risk for subsequent stroke. Magnetic resonance imaging at entry and 2 years will localize and semiquantitatively assess cerebral infarctions and white matter changes. In those patients who come to autopsy during the 5 year duration of the study, neuropathological examination will quantitate the number, location, and volume of cerebral infarctions and assess vascular pathology. These variables will be compared with those of identically assessed healthy controls and Alzheimer disease patients for descriptive features, slope of cognitive change, and correlates of impaired cognition. The application capitalizes on two currently funded projects at Washington University. The R01 "Role of cerebral hemodynamics in ischemic stroke" (NS 28947; RL Grubb, PI) will provide patients at high risk for cerebral infarction (carotid occlusion patients) after completion of their neurological and cerebral hemodynamic assessments. The control and Alzheimer patients will be recruited from the Alzheimer's Disease Research Center (ADRC) AG05681, L Berg, Pl), which also will support this application with resources from its Clinical, Psychometric, Neuropathology and Biostatistics Cores. The ADRC will be the performance site for the longitudinal cognitive and behavioral assessments, the focus of this application.